Abstract
Objectives
To determine the effect of cis-9, trans-11-conjugated linoleic acid on the cell cycle of mammary cancer cells (MCF-7) and its possible mechanism of inhibition cancer growth.
Methods
Using cell culture and immunocytochemical techniques, we examined the cell growth, DNA synthesis, expression of PCNA, cyclin A, B1, D1, p16ink4a and p21cip/wafl of MCF-7 cells which were treated with various c9, t11-CLA concentrations (25 mM, 50 mM, 100 mM and 200 mM) of c9, t11-CLA for 24 and 48 h, with negative controls (0.1% ethanol).
Results
The cell growth and DNA synthesis of MCF-7 cells were inhibited by c9, t11-CLA. MCF-7 cells, after treatment with various c9, t11-CLA doses mentioned above for 8 days, the inhibition frequency was 27.18%, 35.43%, 91.05%, and 92.86%, respectively and the inhibitory effect of c9, t11-CLA on DNA synthesis (except for 25 mM, 24 h) incorporated significantly less3H-TdR than did the negative control (P<0.05 andP<0.01). To further investigate the influence on the cell cycle progression, we found that c9, t11-CLA may arrest the cell cycle of MCF-7 cells. Immunocytochemical staining demonstrated that MCF-7 cells preincubated in media supplemented with different c9, t11-CLA concentrations at various times significantly decreased the expressions of PCNA, and Cyclin, A, B1, D1 compared with the negative controls (P<0.01), whereas the expressions of p16ink4a and p21cip/wafl, cyclin-dependent kinases inhibitors (CDKI), were increased.
Conclusions
The cell growth and proliferation of MCF-7 cells is inhibited by c9, t11-CLA by blocking the cell cycle, which reduces expressions of cyclin A, B1, D1 and enhances expressions of CDKI (p16ink4a and p21cip/wafl).
Key words: mammary adenocarcinoma cells (MCF-7); cis-9; trans-11-conjugated linoleic acid (c9, t11-CLA); immunocytochemistry; cell cycle; inhibition
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